Pharmacokinetic, acute toxicity, and pharmacodynamic studies of semen strychni total alkaloid microcapsules

Purpose: To investigate the safety and effectiveness of semen strychni total alkaloid microcapsules (SSTAM), compared with semen strychni total alkaloids (SSTA). Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed to assess pharmacokinetics of brucine and strychnine in rats. Acute toxicity was investigated in pre-test and formal experiments in mice. The pharmacodynamics of SSTAM and SSTA were evaluated by their analgesic and anti-inflammatory activities. Results: With respect to brucine, the half-life of SSTA group (1.6 mg/kg), low-dose SSTAM group (6 mg/kg) and high-dose SSTAM group (10 mg/kg) was 5.723, 9.321 and 9.025 h, respectively. With respect to strychnine, the half-life of SSTA group, low-dose SSTAM group and high-dose SSTAM group was 4.065, 8.819 and 8.654 h, respectively. The LD50 values of SSTAM group and SSTA group were 236.59 and 30.27 mg/kg, respectively. The pain inhibition rates of SSTAM groups (25 and 50 mg/kg) were higher than that of SSTA group (p < 0.05) while the pain threshold values of the SSTAM groups (25 and 50 mg/kg) were higher than that of blank control (p < 0.01) and SSTA groups (p < 0.01) at 60 min and 120 min. The inhibition rates of the SSTAM groups (25 and 50 mg/kg) were higher than that of SSTA group based on ear swelling and cotton ball granulation tests. Compared with blank control and SSTA groups, the absorbance values of SSTAM groups (25 and 50 mg/kg) were lower (p < 0.01). Conclusion: SSTAM increases the dosage of administration but reducea the toxicity of the alkaloids in rats, and is thus a potentially safe and effective drug delivery system.

Computational and Pharmacological Studies on the Antioxidant, Thrombolytic, Anti-Inflammatory, and Analgesic Activity of Molineria capitulata

Molineria capitulata is an ornamental plant that has traditionally been used to treat several chronic diseases. The present study was designed to examine the antioxidant, cytotoxic, thrombolytic, anti-inflammatory, and analgesic activities of a methanolic extract of M. capitulata leaves (MEMC) using both experimental and computational models. Previously established protocols were used to perform qualitative and quantitative phytochemical screening in MEMC. A computational study, including molecular docking and ADME/T analyses, was performed. The quantitative phytochemical analysis revealed the total phenolic and flavonoid contents as 148.67 and 24 mg/g, respectively. Antioxidant activity was assessed by examining the reducing power of MEMC, resulting in absorbance of 1.87 at 400 µg/mL, demonstrating a strong reduction capacity. The extract exhibited significant protection against blood clotting and showed the highest protein denaturation inhibition at 500 µg/mL. In both the acetic acid-induced writhing and formalin-induced paw-licking models, MEMC resulted in significant potential pain inhibition in mice. In the computational analysis, 4-hydroxybenzaldehyde, orcinol glucoside, curcapital, crassifogenin C, and 2,6-dimethoxy-benzoic acid displayed a strong predictive binding affinity against the respective receptors. These findings indicated that M. capitulata possesses significant pharmacological activities to an extent supported by computational studies.

The inhibitory effect of conditioned pain modulation on temporal summation in low-back pain patients

Objectives The literature on conditioned pain modulation (CPM) is inconclusive in relation to low-back pain and it is unclear how CPM affects temporal summation as a proxy of central pain integration. The aim of this study was to examine whether the CPM effect would be different on pain induced by temporal summation than single stimuli in a group of low back pain patients. Methods A total of 149 low-back pain patients were included. CPM was examined using single, repeated and temporal summation (repeated-single difference) of mechanical pressure pain as test stimuli at an individualized, fixed supra-pain-threshold force, before and after 2 min of cold pressor test (0–2 degrees Celsius). Participants were categorized as CPM responders or non-responders according to three different criteria: simple (any pain inhibition), strict (pain inhibition of more than 10VAS) and reversed (pain inhibition or facilitation of less than 10VAS). Clinical data on back pain was collected for correlation and descriptive purposes. Results Significant modulation was observed for all three test stimuli. Effects sizes were comparable in relative terms, but repeated pressure pain modulation was greater in absolute terms. No correlations to clinical data were observed, for any measure. Conclusions The current data suggests that repeated pressure pain may be better suited as the CPM test stimuli, than single pressure pain and temporal summation of pressure pain, as the CPM effect in absolute terms was greater. Employing temporal summation as the test stimulus in a CPM paradigm may be more sensitive than a single test stimulus.

Transcranial Magnetic Stimulation (TMS) and its cortical targets in the treatment of fibromyalgia: a systematic review

Background: Fibromyalgia (FM) is a non-inflammatory disease with unknown etiology expressed by diffuse musculoskeletal pain, whose definition and management are subjects of controversies. Thus we aimed to review the literature on efficacy and main cortical targets of TMS for FM. Methods: A systematic review was carried out in PubMed databases, along with the terms DeCS/MeSH: “Fibromyalgia AND (Transcranial Magnetic Stimu-lation OR TMS)”. Randomized studies and clinical trials published in the last 10 years were selected. After exclusion, 11 articles remained. Results: The references found for TMS in the treatment of FM indicate average reduction in pain symptoms (29%). TMS showed significant improvement in pain measured by visual analog scale and was more advantageous in clinical and functional improvement, but less efficient in psychiatric conditions. In female patients, active use of repetitive high-frequency TMS was significantly better on pain, quality of life (QoL) and depression. Another study showed that 20 sessions produced significantly lasting pain inhibition and improved QoL when operated at 10 Hz. Moreover, the right dorsolateral prefrontal cortex or the left motor cortex can have antidepressant and pain-modulating effects. Evidence also points to an important improvement in physical and general fatigue, as well as greater chance of clinical improvement in pain intensity. Conclusions: Evidence on TMS for FM available so far is promising, with potential to represent a valuable and safe therapeutic option. However, more and larger studies are needed to elucidate mechanisms and effectiveness better

Inter-individual predictors of pain inhibition during performance of a competing cognitive task

The main function of pain is to automatically draw attention towards sources of potential injury. However, pain sometimes needs to be inhibited in order to address or pursue more relevant tasks. Elucidating the factors that influence how people manage this relationship between pain and task performance is essential to understanding the disruptive nature of pain and its variability between individuals. Here, 41 healthy adults completed a challenging working memory task (2-back task) while receiving painful thermal stimulations. Examining the trial-by-trial relationship between pain perception and task performance revealed that pain’s disruptive effects on performance were mediated by self-reported pain intensity, and that the analgesic effects of a competing task were influenced by task performance. We found that higher pain catastrophizing, higher trait anxiety, and lower trait mindfulness were associated with larger trade-offs between pain perception and task performance, suggesting that these psychological factors can predict increased fluctuations between disruption by pain and analgesia from a competing task. Altogether these findings provide an important and novel perspective on our understanding of individual differences in the interplay between pain and ongoing task performance.

Electrophysiological investigation of the contribution of attention to altered pain inhibition processes in patients with irritable bowel syndrome

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder associated with chronic abdominal pain and altered pain processing. The aim of this study was to examine whether attentional processes contribute to altered pain inhibition processes in patients with IBS. Nine female patients with IBS and nine age-/sex-matched controls were included in a pain inhibition paradigm using counter-stimulation and distraction with electroencephalography. Patients with IBS showed no inhibition of pain-related brain activity by heterotopic noxious counter-stimulation (HNCS) or selective attention. In the control group, HNCS and selective attention decreased the N100, P260 and high-gamma oscillation power. In addition, pain-related high-gamma power in sensorimotor, anterior cingulate and left dorsolateral prefrontal cortex was decreased by HNCS and selective attention in the control group, but not in patients with IBS. These results indicate that the central pain inhibition deficit in IBS reflects interactions between several brain processes related to pain and attention.

Analgesic and anti-inflammatory activity of aqueous extract of Bubonium graveolens

Introduction: Bubonium graveolens is used in traditional pharmacopoeia against imbalances of the gastrointestinal tract, cephalic pains, and bronchitis, and as an anti-inflammatory agent. Methods: We have investigated the analgesic and anti-inflammatory activities of the aqueous extract of Bubonium graveolens in male mice of strain NMRI Albinos, weighing between 22 g and 38 g. Acetic acid was used to induce writhes in the mice and inflammation of paw edema. Results: Evaluation of the analgesic activity showed that the aqueous extract at 150 mg/kg of the plant induced a decrease in the number of abdominal cramps caused by 1% acetic acid. The aqueous extract of the plant had an analgesic effect almost equal to that of Diclofenac; in fact, the latter caused a pain inhibition of 49 ± 1.1% while Bubonium graveolens caused a pain inhibition of 49.6 ± 2.1%, at the concentration of 150 mg/kg. Evaluation of the percentage of inhibition showed that the aqueous extract of Bubonium graveolens had a better anti-inflammatory activity compared to Diclofenac sodium during the treatment duration (69.57% — 56.52% at 60 min; 71.43% — 50.00% at 120 min, and 75.00% — 66.67% at 180 min). Conclusion: The results of this research indicate that Bubonium graveolens inhibits inflammation and could explain its effective use in traditional medicine.